Two continual retinal tumor cell lines (RAO-188 from rat and UAL 1-3 from mouse) have been established in the applicant's laboratory. Since both lines are stable over many passages and are highly transplantable in all syngeneic progenies, they can be used for in vitro and in vivo experiments. When diputyrl cyclic AMP (DBcAMP) is added to the culture media, retinal tumor cells of both lines appear to become differentiated (a sign of ganglioneuronic maturation): 1. Using both undifferentiated and differentiated retinal tumor cells from RAO-188 and UAL 1-3 continual cell lines, we wish to ascertain the clinical applicablity of using urinary concentration of catecholamine and its major byproducts, vanilmandelic acid (VMA) and homovanillic acid (HVA), as an indicator of the degree of differentiation of retinoblastoma cells. If this is feasible, it will contribute to our knowledge of the nature of retinoblastoma cell differentiation and may furnish clues to its prognosis and treatment. (2) After transplanting both cell lines into syngeneic progenies, the effects of cancer chemotherapy - 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), 1-(2-chlo oethyl-3-trans (4-methylcyclohexyl)-1-nitrosourea (CCNU), vincristine, cyclophosphamide, methotrexate, and triethylene melamine (TEM) - will be evaluated by studying changes in tumor cell morphology. (3) Using the rat cell line (RAO-188), isologous tumor cells transplanted into CDF rats will be subjected to a study of humoral immunity in an effort to ascertain the probable cause of spontaneous regression of retinoblastoma. Lymphocytotoxicity tests will provide the basis on which a possible therapy might be devised by stimulating the host immune system.